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Objective To investigate the effect of pioglitazone (PIO) on vascular endothelial cell (VEC) apoptosis induced by the high glucose and its mechanism. Methods The VECs in the logarithmic growth were randomly divided into 6 groups: group A, normal control group (Glu 5.5 mmol/L) ; group B, cultured in high glucose group (Glu 33 mmol/L) ; group C, high glucose +low concentrations PIO group (PIO 1 x 10-8 mmol/L) ; group D, high glucose + middle concentrations PIO group (PIO 1 x 10-6 mmol/L) ; group E, high glucose + high concentrations PIO group (1 x 10-4 mmol/L) ; group F, 10.0 µM SP600125 + PIO group (PIO 1 x 10-4 mmol/L) . The apoptosis rate in each group was measured by Annexin V/PI double staining. The protein expressions of JNK and p-JNK in each group were detected by Western-Blot, and the change of JNK phosphorylation in high glucose-induced vascular endothelial cell under the action of PIO was observed. Results (1) Compared to the high glucose group, middle concentrations PIO (l x 10-6 mmol/L) and high concentrations PIO (l x 10-4 mmol/L) reduced the apoptosis of VEC obviously (P< 0.05), in a dose-dependent manner. (2) PIO obviously decreased the phosphorylation level of JNK in high glucose group (P< 0.05), and in a dose-dependent manner. Compared to high glucose group, JNK inhibitor SP600125 declined the level of phosphrylation, and the difference was significant (P < 0.05) . Conclusion PIO can obviously inhibit VEC apoptosis induced by high glucose, the inhibition effect of PIO may be achieved by affecting the JNK pathway. [ABSTRACT FROM AUTHOR]